title: Ashkenazi-Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect.
abstract: The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive neurological disorder caused by a partial deficiency of beta-hexosaminidase A. We had previously identified, in Ashkenazi-Jewish adult GM2 gangliosidosis patients, a Gly269----Ser mutation in the beta-hexosaminidase alpha-subunit. All of the Ashkenazi patients were found to be compound heterozygotes with an allele containing the Gly269----Ser mutation together with one of the Ashkenazi infantile Tay-Sachs alleles. We have now found the same Gly269----Ser mutation in six adult GM2 gangliosidosis patients from four different non-Jewish families. Genomic DNA from three of the patients, two of whom were brothers, exhibited a hybridization pattern consistent with homozygosity for the Gly269----Ser mutation. The remaining non-Jewish patients were compound heterozygotes of the Gly269----Ser mutation together with an unidentified alpha-subunit mutation. The results demonstrate that individuals homozygous for the Gly269----Ser change can be clinically affected. The same Gly269----Ser mutation in both the Ashkenazi and non-Jewish patients may be the result of a common ancestor, given that the ancestry of these non-Jewish patients, like the Ashkenazim, can be traced to eastern Europe.
authors.affiliation: Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: R
authors.initials: R
authors.lastname: Navon
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: H
authors.initials: H
authors.lastname: Mitsumoto
authors.forename: G H
authors.initials: GH
authors.lastname: Thomas
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D001483:Base Sequence; D015342:DNA Probes; D005260:Female; D005678:G(M2) Ganglioside / Q000235:genetics*; D005732:Gangliosides / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013661:Tay-Sachs Disease / Q000235:genetics*
chemical_list: D015342:DNA Probes; D005732:Gangliosides; D005678:G(M2) Ganglioside